ResearchPad - atherosclerosis https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[High-density lipoprotein remodelled in hypercholesterolaemic blood induce epigenetically driven down-regulation of endothelial HIF-1α expression in a preclinical animal model]]> https://www.researchpad.co/article/elastic_article_15984 Graphical Abstract

]]>
<![CDATA[Homeobox B9 integrates bone morphogenic protein 4 with inflammation at atheroprone sites]]> https://www.researchpad.co/article/elastic_article_15982 Graphical Abstract

]]>
<![CDATA[Association of subclinical atherosclerosis with echocardiographic indices of cardiac remodeling: The Framingham Study]]> https://www.researchpad.co/article/elastic_article_14706 It is well established that coronary artery disease progresses along with myocardial disease. However, data on the association between coronary artery calcium (CAC) and echocardiographic variables are lacking.Methods and resultsAmong 2,650 Framingham Study participants (mean age 51 yrs, 48% women; 40% with CAC>0), we related CT-based CAC score to left ventricular (LV) mass index (LVMi), LV ejection fraction (LVEF), E/e’, global longitudinal strain (GLS), left atrial emptying fraction (LAEF), and aortic root diameter (AoR), using multivariable-adjusted generalized linear models. CAC score (independent variable) was used as log-transformed continuous [ln(CAC+1)] and as a categorical (0, 1–100, and ≥101) variable. Adjusting for standard risk factors, higher CAC score was associated with higher LVMi and AoR (βLVMI per 1-SD increase 0.012, βAoR 0.008; P<0.05, for both). Participants with 1≤CAC≤100 and those with CAC≥101 had higher AoR (βAoR 0.013 and 0.020, respectively, P = 0.01) than those with CAC = 0. CAC score was not significantly associated with LVEF, E/e’, GLS or LAEF. Age modified the association of CAC score with AoR; higher CAC scores were associated with larger AoR more strongly in older (>58 years; βAoR0.0042;P<0.007) than in younger (≤58 years) participants (βAoR0.0027;P<0.03).ConclusionsWe observed that subclinical atherosclerosis was associated with ventricular and aortic remodeling. The prognostic significance of these associations warrants evaluation in additional mechanistic studies. ]]> <![CDATA[Collagen methionine sulfoxide and glucuronidine/LW-1 are markers of coronary artery disease in long-term survivors with type 1 diabetes. The Dialong study]]> https://www.researchpad.co/article/elastic_article_13877 Type 1 diabetes is a risk factor for coronary heart disease. The underlying mechanism behind the accelerated atherosclerosis formation is not fully understood but may be related to the formation of oxidation products and advanced glycation end-products (AGEs). We aimed to examine the associations between the collagen oxidation product methionine sulfoxide; the collagen AGEs methylglyoxal hydroimidazolone (MG-H1), glucosepane, pentosidine, glucuronidine/LW-1; and serum receptors for AGE (RAGE) with measures of coronary artery disease in patients with long-term type 1 diabetes.MethodsIn this cross-sectional study, 99 participants with type 1 diabetes of ≥ 45-year duration and 63 controls without diabetes had either established coronary heart disease (CHD) or underwent Computed Tomography Coronary Angiography (CTCA) measuring total, calcified and soft/mixed plaque volume. Skin collagen methionine sulfoxide and AGEs were measured by liquid chromatography-mass spectrometry and serum sRAGE/esRAGE by ELISA.ResultsIn the diabetes group, low levels of methionine sulfoxide (adjusted for age, sex and mean HbA1c) were associated with normal coronary arteries, OR 0.48 (95% CI 0.27–0.88). Glucuronidine/LW-1 was associated with established CHD, OR 2.0 (1.16–3.49). MG-H1 and glucuronidine/LW-1 correlated with calcified plaque volume (r = 0.23–0.28, p<0.05), while pentosidine correlated with soft/mixed plaque volume (r = 0.29, p = 0.008), also in the adjusted analysis.ConclusionsLow levels of collagen-bound methionine sulfoxide were associated with normal coronary arteries while glucuronidine/LW-1 was positively associated with established CHD in long-term type 1 diabetes, suggesting a role for metabolic and oxidative stress in the formation of atherosclerosis in diabetes. ]]> <![CDATA[Paleogenetic study on the 17th century Korean mummy with atherosclerotic cardiovascular disease]]> https://www.researchpad.co/article/5aafccf3463d7e7f05234537

While atherosclerotic cardiovascular disease (ASCVD) is known to be common among modern people exposed to various risk factors, recent paleopathological studies have shown that it affected ancient populations much more frequently than expected. In 2010, we investigated a 17th century Korean female mummy with presumptive ASCVD signs. Although the resulting report was a rare and invaluable conjecture on the disease status of an ancient East Asian population, the diagnosis had been based only on anatomical and radiological techniques, and so could not confirm the existence of ASCVD in the mummy. In the present study, we thus performed a paleogenetic analysis to supplement the previous conventional diagnosis of ASCVD. In aDNA extracted from the same Korean mummy, we identified the risk alleles of seven different SNPs (rs5351, rs10757274, rs2383206, rs2383207, rs10757278, rs4380028 and rs1333049) that had already been revealed to be the major risk loci of ASCVD in East Asian populations. The reliability of this study could be enhanced by cross-validation using two different analyses: Sanger and SNaPshot techniques. We were able to establish that the 17th century Korean female had a strong genetic predisposition to increased risk of ASCVD. The current paleogenetic diagnosis, the first of its kind outside Europe, re-confirms its utility as an adjunct modality for confirmatory diagnosis of ancient ASCVD.

]]>
<![CDATA[Opposing effects of HNP1 (α-defensin-1) on plasma cholesterol and atherogenesis]]> https://www.researchpad.co/article/Ndf7081dd-c312-4392-aa9c-ddf6cf67dfa0

Atherosclerosis, the predominant cause of death in well-resourced countries, may develop in the presence of plasma lipid levels within the normal range. Inflammation may contribute to lesion development in these individuals, but the underlying mechanisms are not well understood. Transgenic mice expressing α-def-1 released from activated neutrophils develop larger lipid and macrophage-rich lesions in the proximal aortae notwithstanding hypocholesterolemia caused by accelerated clearance of α-def-1/low-density lipoprotein (LDL) complexes from the plasma. The phenotype does not develop when the release of α-def-1 is prevented with colchicine. However, ApoE-/- mice crossed with α-def-1 mice or given exogenous α-def-1 develop smaller aortic lesions associated with reduced plasma cholesterol, suggesting a protective effect of accelerated LDL clearance. Experiments were performed to address this seeming paradox and to determine if α-def-1 might provide a means to lower cholesterol and thereby attenuate atherogenesis. We confirmed that exposing ApoE-/- mice to α-def-1 lowers total plasma cholesterol and decreases lesion size. However, lesion size was larger than in mice with total plasma cholesterol lowered to the same extent by inhibiting its adsorption or by ingesting a low-fat diet. Furthermore, α-def-1 levels correlated independently with lesion size in ApoE-/- mice. These studies show that α-def-1 has competing effects on atherogenesis. Although α-def-1 accelerates LDL clearance from plasma, it also stimulates deposition and retention of LDL in the vasculature, which may contribute to development of atherosclerosis in individuals with normal or even low plasma levels of cholesterol. Inhibiting α-def-1 may attenuate the impact of chronic inflammation on atherosclerotic vascular disease.

]]>
<![CDATA[Matrix Metalloproteinases in COPD and atherosclerosis with emphasis on the effects of smoking]]> https://www.researchpad.co/article/5c785018d5eed0c484007c7f

Background

Matrix metalloproteinases (MMP´s) are known biomarkers of atherosclerosis. MMP´s are also involved in the pathophysiological processes underlying chronic obstructive pulmonary disease (COPD). Cigarette smoking plays an important role in both disease states and is also known to affect the concentration and activity of MMP´s systemically. Unfortunately, the epidemiological data concerning the value of MMP´s as biomarkers of COPD and atherosclerosis with special regards to smoking habits are limited.

Methods

450 middle-aged subjects with records of smoking habits and tobacco consumption were examined with comprehensive spirometry, carotid ultrasound examination and biomarker analysis of MMP-1, -3, -7, -10 and -12. Due to missing data 33 subjects were excluded.

Results

The remaining 417 participants were divided into 4 different groups. Group I (n = 157, no plaque and no COPD), group II (n = 136, plaque but no COPD), group III (n = 43, COPD but no plaque) and group IV (n = 81, plaque and COPD). Serum levels of MMP-1,-7,-10-12 were significantly influenced by smoking, and MMP-1, -3, -7 and-12 were elevated in subjects with COPD and carotid plaque. This remained statistically significant for MMP-1 and-12 after adjusting for traditional risk factors.

Conclusion

COPD and concomitant plaque in the carotid artery were associated with elevated levels of MMP-1 and -MMP-12 even when adjusting for risk factors. Further studies are needed to elucidate if these two MMP´s could be useful as biomarkers in a clinical setting. Smoking was associated with increased serum levels of MMP´s (except for MMP-3) and should be taken into account when interpreting serum MMP results.

]]>
<![CDATA[Subclinical atherosclerosis in psoriasis. Usefulness of femoral artery ultrasound for the diagnosis, and analysis of its relationship with insulin resistance]]> https://www.researchpad.co/article/5c6730cfd5eed0c484f38183

Background

Psoriasis is associated with an increased risk of cardiovascular disease (CVD) at younger ages that is not identifiable by traditional risk factors. Screening for subclinical atherosclerosis with ultrasound has only been investigated in carotid arteries. Femoral artery ultrasound has never been considered for this purpose. The link between psoriasis and accelerated atherosclerosis has not yet been established.

Objective

To study the usefulness of femoral artery ultrasound for the detection of subclinical atherosclerosis in psoriasis. We also investigated its possible relationship with changes in insulin resistance.

Methods

We conducted a cross-sectional study in 140 participants, 70 patients with moderate-to-severe psoriasis and 70 healthy controls, matched 1:1 for age, sex, and BMI. Femoral and carotid atherosclerotic plaques were evaluated by ultrasonography. Insulin resistance was assessed by the homeostasis model assessment method (HOMA-IR).

Results

Femoral atherosclerotic plaque prevalence was significantly higher in patients with psoriasis (44.64%) than in controls (19.07%) (p<0.005), but no significant difference was found in carotid plaque prevalence (p<0.3). Femoral plaques were significantly more prevalent than carotid plaques (21.42%) among patients with psoriasis (p<0.001). In the regression analysis, insulin resistance was the most influential determinant of atherosclerosis in psoriasis and C-reactive protein the most significant predictor of insulin resistance.

Conclusions

Ultrasound screening for femoral atherosclerotic plaques improves the detection of subclinical atherosclerosis in patients with psoriasis, whereas the study of carotid arteries is not sufficiently accurate. Insulin resistance appears to play a greater role in the development of atherosclerosis in these patients in comparison to other classical CVD risk factors.

]]>
<![CDATA[The association of CHA2DS2-VASc score and carotid plaque in patients with non-valvular atrial fibrillation]]> https://www.researchpad.co/article/5c673079d5eed0c484f37bb6

Objective

The aim of this study was to assess the association between CHA2DS2-VASc score and carotid plaques in patients with non-valvular atrial fibrillation (NVAF).

Methods

We conducted a retrospective study including 3,435 NVAF patients who underwent carotid ultrasound examinations from January 2015 to December 2017.We collected the clinical data on the medical records system. Chi-square trend test was used to analyze trends between the prevalence of carotid plaques with an increasing CHA2DS2-VASc score. Univariate and multivariate logistic regression was also used to assess the association between carotid plaques and CHA2DS2-VASc scores. The area under the receiver operating characteristic (ROC) curve (AUC) was used to determine the optimal cutoff points of different CHA2DS2-VASc scores in NVAF patients.

Results

NVAF patients with carotid plaques had higher CHA2DS2-VASc scores compared with patients who did not have carotid plaques (3.01±1.36 vs. 2.55±1.28, P < 0.05). In all participants, male participants and female participants, the prevalence of carotid plaques increased significantly as the CHA2DS2-VASc score increased (P for trend < 0.001). Multivariate logistic regression analysis demonstrated that for each 1-point increase in the CHA2DS2-VASc score, there was an associated 37% increase in the prevalence of carotid plaques. ROC curve analysis revealed that a CHA2DS2-VASc score ≥ 2 in male patients (sensitivity, 44.67%; specificity, 75.64%; AUC, 0.639) or ≥ 3 in female patients (sensitivity, 47.24%; specificity, 72.40%; AUC, 0.634) were associated with carotid plaques.

Conclusion

The prevalence of carotid plaques in patients with NVAF was associated with the CHA2DS2-VASc score.

]]>
<![CDATA[Equilin in conjugated equine estrogen increases monocyte-endothelial adhesion via NF-κB signaling]]> https://www.researchpad.co/article/5c5b5254d5eed0c4842bc66d

The adhesion of monocytes to endothelial cells, which is mediated by adhesion molecules, plays a crucial role in the onset of atherosclerosis. Conjugated equine estrogen, which is widely used for estrogen-replacement therapy, contains both estrone sulfate and various nonhuman estrogens, including equilin. To investigate the association between various estrogen types and atherosclerosis risk, we examined their effect on adhesion-molecule expression in human umbilical vein endothelial cells (HUVECs). In estrogen-treated HUVECs, the mRNA and protein expression levels of adhesion molecules were quantified by real-time polymerase chain reaction and enzyme immunoassay. Additionally, a flow-chamber system was used to assess the effects of estrogens on the adherence of U937 monocytoid cells to HUVECs. Equilin, but not 17β-estradiol (E2) or other types of estrogen, significantly increased the mRNA (P < 0.01) and protein (P < 0.05) expression of the adhesion molecules E-selectin and intercellular adhesion molecule-1 as compared with levels in controls. Equilin treatment increased the adherence of U937 monocytoid cells to HUVECs relative to the that in the control (P < 0.05), decreased estrogen receptor (ER)β expression, and increased the expression of proteins involved in nuclear factor kappa-B (NF-κB) activation relative to levels in controls. Furthermore, the accumulation of NF-κB subunit p65 in HUVEC nuclei was promoted by equilin treatment. By contrast, E2 treatment neither increased the number of adhered monocytoid cells to HUVECs nor altered the expression of ERβ or NF-κB-activating proteins. Our findings suggest that in terms of the adhesion of monocytes at the onset of atherosclerosis, E2 may be preferable for estrogen-replacement therapy. Further studies comparing equilin treatment with that of E2 are needed to investigate their differential impacts on atherosclerosis.

]]>
<![CDATA[Reproducibility and validity of a novel invasive method of assessing peripheral microvascular vasomotor function]]> https://www.researchpad.co/article/5c57e6ddd5eed0c484ef3ffe

In healthy arteries, blood flow is regulated by microvascular tone assessed by changes in blood flow volume and vascular resistance to endothelium-dependent and -independent vasodilators. We developed a novel method of using intravascular ultrasound (IVUS) and a Doppler flow wire to measure changes in blood flow volume and vascular resistance of the profunda arterial bed. We assessed the variability over 6 months in measuring microvascular endothelium-dependent dilation to acetylcholine and endothelium-independent dilation to adenosine in 20 subjects who were part of a larger study of Gulf War Illness without obstructive peripheral artery disease. Vasomotor function was assessed by Infusions of control (dextrose), acetylcholine (10-6M), adenosine (50μg), and nitroglycerin (25μg/ml). 400 IVUS and 240 flow velocity images were measured a mean 6 (SD = 2) months apart blind to measurement and infusion stage. The mean (SD) baseline profunda flow was 227 (172) ml/min and vascular resistance 4.6 x 104 (2.4 x 104) dynes-s/cm5. The intraclass correlation coefficients for 6-month variability for vascular function were excellent (range 0.827–0.995). Bland-Altman analyses showed mean differences of less than 2% for microvascular endothelium-dependent function (flow volume and resistance) and less than 1% for macrovascular endothelium-dependent function with acceptable limits of agreement. In 49 subjects assessing concurrent validity of the technique against atherosclerosis risk factors, we observed greater impairment in microvascular endothelium-dependent function per year of age (flow volume = -1.4% (p = 0.018), vascular resistance = 1.5% (p = 0.015)) and current smoking (flow volume = -36.7% (p = .006), vascular resistance = 50.0% (p<0.001)). This novel method of assessing microvascular vasomotor function had acceptable measurement reproducibility and validity.

]]>
<![CDATA[Thoracic aortic calcification across the clinical dysglycemic continuum in a large Asian population free of cardiovascular symptoms]]> https://www.researchpad.co/article/5c390bffd5eed0c48491f53e

Thoracic aortic calcification (TAC) is tightly linked to pathological atherosclerosis and associated with certain cardiovascular diseases. While diabetes mellitus (DM) is known as a coronary heart disease equivalent, we examined the presence of TAC across the dysglycemic spectrum of diabetes mellitus (DM). We consecutively studied 3003 asymptomatic ethnic Asians underwent annual cardiovacular health survey, and further categorized them into: 1) 1760 normo-glycemic, 2) 968 pre-diabetic, and 3) 274 overt DM based on dysglycemic indices and medical histories. Several TAC parameters were assessed using non-contrast multi-detector computed tomography (MDCT), and related to dysglycemic indices or diabetes mellitus status. A remarkably graded increases of adjusted total TAC calcium burden, volume and density were seen across Non-diabetes, Pre-diabetes, and diabetes mellitus categories and positively correlated with all dysglycemic profiles (all p<0.001). Multi-variate logistic and linear regression models demonstrated independent associations between greater TAC density and all dysglycemic indices (Coef: 2.5, 1.4, 6.8 for fasting, postprandial sugar and HbA1c) and diabetes mellitus status (all p<0.05). Furthermore, Receiver-operating characteristic curves (ROC) showed fasting sugar and postprandial sugar set at 103mg/dL and 111mg/dL, separately, with HbA1c set at 5.8% all predict the presence of aortic calcification. Dysglycemic status, even without overt diabetes mellitus, were tighly linked to subclinical, pathological thoracic aortic calcification.

]]>
<![CDATA[Liver steatosis and dyslipidemia after HCV eradication by direct acting antiviral agents are synergistic risks of atherosclerosis]]> https://www.researchpad.co/article/5c26972cd5eed0c48470ed67

Aim

We comprehensively analyzed how hepatitis C virus (HCV) eradication by interferon (IFN)-free direct-acting-antiviral-agents (DAAs) affects liver steatosis and atherogenic risk.

Methods

Patients treated with IFN-free-DAAs who underwent transient elastography before and at 24-weeks post-treatment, including controlled attenuation parameter (CAP), and achieved sustained viral response (SVR) were enrolled. The association between changes in liver steatosis, lipid-metabolism, and genetic and clinical factors was analyzed.

Results

A total of 117 patients were included. The mean CAP and low-density lipoprotein cholesterol (LDL-C) levels were significantly elevated at SVR24. However, baseline LDL-C and CAP values were significantly negatively correlated with changes in these values after HCV eradication, indicating that in patients with high baseline values, the values generally decreased after HCV eradication. Mean small-dense LDL-C (sdLDL-C), which has greater atherogenic potential, was significantly elevated only in patients with both dyslipidemia (LDL-C >140 mg/dL) and liver steatosis (CAP >248 dB/m) at SVR24. Those patients had significant higher baseline BMI, LDL-C, and total-cholesterol levels.

Conclusions

Generally, successful HCV eradication by IFN-free-DAAs decreases CAP and LDL-C in patients with high baseline values. However, elevated LDL-C was accompanied with elevated sdLDL-C only in patients with liver steatosis and dyslipidemia at SVR24; therefore, those patients may require closer monitoring.

]]>
<![CDATA[Nerve conduction velocity is negatively associated with intima-media thickness and brachial-ankle pulse wave velocity in men with type 2 diabetes mellitus]]> https://www.researchpad.co/article/5c254566d5eed0c48442c6a7

Objective

Previous studies suggest that the presence of diabetic peripheral polyneuropathy (DPN) is associated with atherosclerotic diseases; however, little is known about the relationship between diabetic nerve conduction velocity (NCV) versus arterial stiffness and atherosclerosis parameters.

Methods

The subjects in this study were 292 men with type 2 diabetes mellitus (T2DM). All subjects underwent NCV examination at median and tibial nerves as motor nerve (MCV) as well as median and sural nerves as sensory nerve (SCV). Brachial-ankle pulse wave velocity (baPWV) and carotid intima-media thickness (IMT) were evaluated as arterial stiffness and atherosclerosis parameters.

Results

Pearson’s correlation coefficient showed that NCV at all sites negatively correlated with baPWV, maximal and mean IMT (IMT-Max and IMT-Mean), and plaque score (all p values p<0.01 at least). Multiple regression analyses adjusted for confounding factors such as age, duration of diabetes, body mass index, HbA1c, fasting C-peptide, systolic blood pressure, HDL-cholesterol, LDL-cholesterol and albuminuria showed that the association of NCV with IMT-Max, ITM-Mean, and plaque score remained significant (all p values p<0.05 at least) except that between SCV at median and IMT-Max. Moreover, SCV at median (forearm) and sural were significantly associated with baPWV (p = 0.023 and p = 0.027, respectively).

Conclusion

The present study showed that DPN estimated by quantitative NCV is linearly associated with the deterioration of arterial stiffness and atherosclerosis parameters in T2DM independently of various diabetic and atherosclerotic factors.

]]>
<![CDATA[Reproducibility of quantitative coronary computed tomography angiography in asymptomatic individuals and patients with acute chest pain]]> https://www.researchpad.co/article/5c1d5b59d5eed0c4846eb6cb

Purpose

Quantitative computed tomography (QCT) provides important prognostic information of coronary atherosclerosis. We investigated intraobserver and interobserver QCT reproducibility in asymptomatic individuals, patients with acute chest pain without acute coronary syndrome (ACS), and patients with acute chest pain and ACS.

Methods

Fifty patients from each cohort, scanned between 01/02/2010-14/11/2013 and matched according to age and gender, were retrospectively assessed for inclusion. Patients with no coronary artery disease, previous coronary artery bypass graft surgery, and poor image quality were excluded. Coronary atherosclerosis was measured semi-automatically by 2 readers. Reproducibility of minimal lumen area (MLA), minimal lumen diameter (MLD), area stenosis, diameter stenosis, vessel remodeling, plaque eccentricity, plaque burden, and plaque volumes was assessed using concordance correlation coefficient (CCC), Bland-Altman, coefficient of variation, and Cohen’s kappa.

Results

A total of 84 patients (63 matched) were included. Intraobserver and interobserver reproducibility estimates were acceptable for MLA (CCC = 0.94 and CCC = 0.91, respectively), MLD (CCC = 0.92 and CCC = 0.86, respectively), plaque burden (CCC = 0.86 and CCC = 0.80, respectively), and plaque volume (CCC = 0.97 and CCC = 0.95, respectively). QCT detected area and diameter stenosis ≥50%, positive remodeling, and eccentric plaque with moderate-good intraobserver and interobserver reproducibility (kappa: 0.64–0.66, 0.69–0.76, 0.46–0.48, and 0.41–0.62, respectively). Reproducibility of plaque composition decreased with decreasing plaque density (intraobserver and interobserver CCC for dense calcium (>0.99; 0.98), fibrotic (0.96; 0.93), fibro-fatty (0.95; 0.91), and necrotic core tissue (0.89; 0.84). Reproducibility generally decreased with worsening clinical risk profile.

Conclusions

Semi-automated QCT of coronary plaque morphology is reproducible, albeit with some decline in reproducibility with worsening patient risk profile.

]]>
<![CDATA[Association between number of children and carotid intima-media thickness in Bangladesh]]> https://www.researchpad.co/article/5c06f03ad5eed0c484c6d459

Previous studies on the association between number of children and carotid intima-media thickness (cIMT) were limited to Western populations. Pregnancy in women is associated with physiologic changes that may influence the risk of cardiovascular disease. Comparing the association between number of children and cIMT in men and women can provide insights on whether the association may be due to pregnancy. We investigated the association between number of children and cIMT among 718 female (mean age 37.5 years) and 417 male participants (mean age 41.3 years), randomly selected from the Health Effect of Arsenic Longitudinal Study (HEALS), a population-based cohort study in Bangladesh. Multivariate linear regression was used to assess the association and to control for education attainment, history of diabetes, age, smoking, betel use, BMI, systolic blood pressure, and diastolic blood pressure. The average number of children was 4.43 for women and 3.74 for men. There were no nulliparous women. We observed a positive association between number of children and cIMT in women. Mean cIMT increased by 4.5 μm (95% CI, 0.8–8.1) per increment of one birth (P = 0.02). Compared to women with two children, cIMT in women with 4 children and ≥5 children was 23.6μm (95%CI, 2.6–44.7; P = 0.03) and 25.1 μm (95%CI, 3.5–46.6; P = 0.02) greater, respectively. The association was not modified by BMI, SBP, betel use or age. Data in men showed no evidence of association (P = 0.4). The finding suggests a role of high parity in atherosclerosis in women of a low-income, high parity population.

]]>
<![CDATA[Age-related macular degeneration and progression of coronary artery calcium: The Multi-Ethnic Study of Atherosclerosis]]> https://www.researchpad.co/article/5b601751463d7e3bf2e777ce

Background

Age-related macular degeneration (AMD) shares many similarities with cardiovascular disease (CVD) pathophysiology. We sought to determine the relationship of AMD to the progression of coronary artery calcium (CAC) using data from the Multi-Ethnic Study of Atherosclerosis (MESA).

Methods

Our cohort consisted of 5803 adults aged 45 to 84 years free of known cardiovascular disease (CVD). Retinal photographs were taken during visit 2 (Aug 2002-Jan 2004). CAC was measured with computed tomography at visit 1 (July 2000-Aug 2002) and visit 5 (April 2010-Dec 2011) and changes between visits were determined.

Results

Participants were categorized as with (n = 244) and without AMD (n = 5559) at visit 2. At visit 5, 92 participants with and 2684 without AMD had CAC scores. Among those with detectable CAC at baseline (>0 at visit 1), CAC progression was greater in persons with compared to those without AMD after multivariable adjustment (530 ± 537 vs. 339 ± 426 Agatston units, P<0.01).

Conclusions

The presence of AMD in a diverse population without known clinical CVD independently predicted higher 10-year CAC progression in participants with baseline CAC >0. The retinal exam might be a useful tool for pre-clinical assessment and prevention of CVD events.

]]>
<![CDATA[Helminth Infections, Type-2 Immune Response, and Metabolic Syndrome]]> https://www.researchpad.co/article/5989da83ab0ee8fa60b9b441 ]]> <![CDATA[A Novel MMP12 Locus Is Associated with Large Artery Atherosclerotic Stroke Using a Genome-Wide Age-at-Onset Informed Approach]]> https://www.researchpad.co/article/5989da2cab0ee8fa60b82acb

Genome-wide association studies (GWAS) have begun to identify the common genetic component to ischaemic stroke (IS). However, IS has considerable phenotypic heterogeneity. Where clinical covariates explain a large fraction of disease risk, covariate informed designs can increase power to detect associations. As prevalence rates in IS are markedly affected by age, and younger onset cases may have higher genetic predisposition, we investigated whether an age-at-onset informed approach could detect novel associations with IS and its subtypes; cardioembolic (CE), large artery atherosclerosis (LAA) and small vessel disease (SVD) in 6,778 cases of European ancestry and 12,095 ancestry-matched controls. Regression analysis to identify SNP associations was performed on posterior liabilities after conditioning on age-at-onset and affection status. We sought further evidence of an association with LAA in 1,881 cases and 50,817 controls, and examined mRNA expression levels of the nearby genes in atherosclerotic carotid artery plaques. Secondly, we performed permutation analyses to evaluate the extent to which age-at-onset informed analysis improves significance for novel loci. We identified a novel association with an MMP12 locus in LAA (rs660599; p = 2.5×10−7), with independent replication in a second population (p = 0.0048, OR(95% CI) = 1.18(1.05–1.32); meta-analysis p = 2.6×10−8). The nearby gene, MMP12, was significantly overexpressed in carotid plaques compared to atherosclerosis-free control arteries (p = 1.2×10−15; fold change = 335.6). Permutation analyses demonstrated improved significance for associations when accounting for age-at-onset in all four stroke phenotypes (p<0.001). Our results show that a covariate-informed design, by adjusting for age-at-onset of stroke, can detect variants not identified by conventional GWAS.

]]>
<![CDATA[Combination Treatment of Rosuvastatin or Atorvastatin, with Regular Exercise Improves Arterial Wall Stiffness in Patients with Coronary Artery Disease]]> https://www.researchpad.co/article/5989da16ab0ee8fa60b7b619

Objective

Statin- and exercise-therapy are both clinically beneficial by preventing cardiovascular events in patients with coronary artery disease (CAD). However, there is no information on the vascular effects of the combination of statins and exercise on arterial wall stiffness in CAD patients.

Methods

The present study is a sub-analysis of PRESET study that determined the effects of 20-week treatment with statins (rosuvastatin, n = 14, atorvastatin, n = 14) combined with regular exercise on arterial wall stiffness assessed by measurement of brachial and ankle pulse wave velocity (baPWV) in CAD patients.

Results

The combination of statins and regular exercise significantly improved exercise capacity, lipid profile, including low- and high-density lipoprotein cholesterol, and high-sensitivity C-reactive protein (hs-CRP), baPWV (baseline: 1747±355, at 20 weeks of treatment: 1627±271 cm/s, p = 0.008), and basophil count (baseline: 42±32, 20 weeks: 26±15 cells/µL, p = 0.007), but had no effect on blood pressure (baseline: 125±22, 20 weeks: 121±16 mmHg). Changes in baPWV correlated significantly with changes in basophil count (r = 0.488, p = 0.008), but not with age, lipids profile, exercise capacity, or hs-CRP.

Conclusion

In CAD patients, the combination treatment with statins and exercise resulted in significant amelioration of arterial wall stiffness, at least in part, through reduction of circulating basophils.

]]>